Summary: Objectives: Although pertussis vaccines containing a whole-cell pertussis component effectively controlled pertussis disease in the US, safety concerns led to an international research and development effort that resulted in the US licensure in 1996-1998 of four DTP products with an acellular pertussis component. Progress in the development and licensing of less reactogenic acellular pertussis vaccines, as well as combination vaccines containing an acellular pertussis component, was hindered by the lack of a laboratory correlate of clinical protection and of standardized assays for measurement of immune responses. To address this need, the Laboratory has continued a long-term research project with the following aims: a) To work toward the international standardization of immunoassays used to evaluate the antigen and isotype specific responses to Bordetella pertussis. b) To employ these assays to evaluate the serologic response in individuals immunized with pertussis vaccine. c) To develop new assays to measure human immune response to vaccine. d) To investigate new animal models that may provide a laboratory correlate of clinical protection. e) To establish suitable vaccine potency assays. FY01 activities: 1) Continued evaluation of a mouse leukocytosis model which is able to detect pertussis toxin (PT)-neutralizing antibodies in serum, and to correlate these results with the anti-PT binding activity of the same sera, as measured by ELISA. This model has been applied to the study of the differential immunogenicity in mice of inactivated pertussis toxin contained in licensed DTaP vaccines 2) Participated in an international, multicenter collaborative study to establish a Pertussis Toxin Reference for the European Pharmacopoeia. As part of this project, performed triplicate assays on a sample provided by the organizers. 3) Organized an international workshop, in collaboration with WHO, to evaluate the status of pertussis vaccine regulations and the availability and needs of reference materials. 4) For an ongoing NIAID study, completed analysis of a sub-group of individuals (n = 110) who received one of 6 different acellular vaccines for all five doses in the series. Our laboratory took a lead role in the analyses of the immunogenicity data over the five dose series. 5) Continued evaluation of the data from a previously published international collaborative study that evaluated immunoassays used in acellular pertussis vaccine efficacy and immunogenicity studies. The goal is to determine which statistical models most accurately describe and define ELISA assay variability.